Hypoxia-Induced Mesenchymal Stem Cell Exosomes Modulate Protein Kinase A and VEGFR Expression in Ultraviolet B-Induced Hyperpigmentation in Mice

Background: Hyperpigmentation is often exacerbated by ultraviolet-B (UVB) exposure through oxidative stress and activation of pathways like mitogen-activated protein kinase (MAPK) and vascular endothelial growth factor receptor (VEGFR). Current treatments carry risks and necessitate safer alternativ...

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Main Authors: Sheila Jessica Andavania, Mas Rizky Syamsunarno, Agung Putra, Eko Setiawan
Format: Article
Language:English
Published: Cell and BioPharmaceutical Institute 2025-07-01
Series:MCBS (Molecular and Cellular Biomedical Sciences)
Online Access:https://cellbiopharm.com/ojs/index.php/MCBS/article/view/594
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Summary:Background: Hyperpigmentation is often exacerbated by ultraviolet-B (UVB) exposure through oxidative stress and activation of pathways like mitogen-activated protein kinase (MAPK) and vascular endothelial growth factor receptor (VEGFR). Current treatments carry risks and necessitate safer alternatives. This study investigated the therapeutic potential of hypoxia-induced mesenchymal stem cell (MSC) exosomes in reducing protein kinase-A (PKA) and VEGFR expression in UVB-induced hyperpigmentation. Materials and methods: A post-test-only control group design was used with 30 male C57BL/6 mice divided into five groups: Healthy group, 0,9% NaCl-treated group, retinol-treated group, and two treatment groups (200 µL Exosomes-treated group and 300 µL Exosomes-treated group. UVB-induced hyperpigmentation was established with 180 mJ/cm² exposures over two weeks. Treatment was administered via subcutaneous injections for seven days. PKA and VEGFR mRNA levels were analyzed using qRT-PCR. Results: PKA expression was significantly lower in the 200 µL Exosomes-treated group (0.34±0.05) and 300 µL Exosomes-treated group (0.21±0.04) groups compared with the 0,9% NaCl-treated group (1.12±0.08) (p<0.001). VEGFR expression similarly decreased in 200 µL Exosomes-treated group (0.32±0.05) and 300 µL Exosomes-treated group (0.18±0.04) versus the 0,9% NaCl-treated group (1.48±0.09) (p<0.001). Both exosome doses achieved reductions comparable to baseline levels observed in the Healthy group. Conclusion: Hypoxia-induced MSC exosomes reduced PKA and VEGFR expression in UVB-induced hyperpigmentation, with the 300 µL dose showing greater efficacy. These findings suggested exosome therapy as a promising alternative for hyperpigmentation treatment.  Keywords: hyperpigmentation, MSC, PKA, VEGFR, melanin
ISSN:2527-4384
2527-3442